Mother-to-infant transmission in developed countries has nearly been "nearly" eliminated following the widespread use of highly active anti-retroviral therapy. This is not true, however, in the developing world where about 30% of the infections in Africa, India and parts of the Near East are from mother to infant. Interestingly, not all infections are transmitted to infants from infected mothers suggesting that barriers in trans placental viral transmission occur or that specific viral variants have differential abilities to infect infants. We posit that select viral variants may be transmitted from mother to infant according to the capacity of the variant to infect placental cells. Moreover, we posit that genetic signatures of the host would determine the susceptibilities for viral infection in the placenta. In support of this idea, reports have shown that in 90% of the cases studied, the placenta successfully shields HIV infection from mother to fetus. In order to explore the mechanisms involved in inhibiting maternal-fetal transmission of HIV we have isolated placental macrophages (PM) and showed that they could be infected with R5 and X4 isolates that are either laboratory adapted or from primary cells from infected mothers. In addition, we developed proteomics techniques to assay cellular protein profiles that may restrict viral infection in virus susceptible PM. Our hypothesis is that anti-retroviral proteins expressed by PM restrict viral replication and in turn limit viral transmission. Using a newly developed proteomics facility at the University of Puerto Rico, combined with our abilities to obtain rapid sequencing of proteins through ongoing collaborations with scientists at the University of Nebraska Medical Center (UNMC) (Drs. Howard Gendelman and Kimberly Carlson), we will assess "putative" anti-retroviral proteins produced from PM. Monocytes will be used as controls for comparative assays. Identified proteins when demonstrated will be tested, in select virus-infection assays, for their influence on viral replication. These experiments would provide unique insights into host cellular immune responses that restrict transmission. This ongoing support, together with our sustained track record in HIV-macrophage biology and newly acquired proteomics experience at the University of Puerto Rico (X. Lou et al. Neurology in press), provide support for the proposed works.